PMID- 28663724
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - Activation of Transient Receptor Potential Vanilloid 4 Impairs the Dendritic 
      Arborization of Newborn Neurons in the Hippocampal Dentate Gyrus through the AMPK 
      and Akt Signaling Pathways.
PG  - 190
LID - 10.3389/fnmol.2017.00190 [doi]
LID - 190
AB  - Neurite growth is an important process for the adult hippocampal neurogenesis 
      which is regulated by a specific range of the intracellular free Ca(2+) 
      concentration ([Ca(2+)](i)). Transient receptor potential vanilloid 4 (TRPV4) is 
      a calcium-permeable channel and activation of it causes an increase in 
      [Ca(2+)](i). We recently reported that TRPV4 activation promotes the 
      proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The 
      present study aimed to examine the effect of TRPV4 activation on the dendrite 
      morphology of newborn neurons in the adult hippocampal DG. Here, we report that 
      intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days 
      (GSK1016790A-injected mice) reduced the number of doublecortin immunopositive 
      (DCX(+)) cells and DCX(+) fibers in the hippocampal DG, showing the impaired 
      dendritic arborization of newborn neurons. The phosphorylated AMP-activated 
      protein kinase (p-AMPK) protein level increased from 30 min to 2 h, and then 
      decreased from 1 to 5 days after GSK1016790A injection. The phosphorylated 
      protein kinase B (p-Akt) protein level decreased from 30 min to 5 days after 
      GSK1016790A injection; this decrease was markedly attenuated by the AMPK 
      antagonist compound C (CC), but not by the AMPK agonist AICAR. Moreover, the 
      phosphorylated mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 
      (p70S6k) protein levels were decreased by GSK1016790A; these changes were 
      sensitive to 740 Y-P and CC. The phosphorylation of glycogen synthase kinase 3beta 
      (GSK3beta) at Y(216) was increased by GSK1016790A, and this change was accompanied 
      by increased phosphorylation of microtubule-associated protein 2 (MAP2) and 
      collapsin response mediator protein-2 (CRMP-2). These changes were markedly 
      blocked by 740 Y-P and CC. Finally, GSK1016790A-induced decrease of DCX(+) cells 
      and DCX(+) fibers was markedly attenuated by 740 Y-P and CC, but was unaffected 
      by AICAR. We conclude that TRPV4 activation impairs the dendritic arborization of 
      newborn neurons through increasing AMPK and inhibiting Akt to inhibit the 
      mTOR-p70S6k pathway, activate GSK3beta and thereby result in the inhibition of MAP2 
      and CRMP-2 function.
FAU - Tian, Yujing
AU  - Tian Y
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
FAU - Qi, Mengwen
AU  - Qi M
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
FAU - Wang, Zhouqing
AU  - Wang Z
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
FAU - Wu, Chunfeng
AU  - Wu C
AD  - Department of Neurology, Children's Hospital of Nanjing Medical 
      UniversityNanjing, China.
FAU - Sun, Zhen
AU  - Sun Z
AD  - Department of Tangshan Branch, Jinling Hospital, Nanjing UniversityNanjing, 
      China.
FAU - Li, Yingchun
AU  - Li Y
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
FAU - Sha, Sha
AU  - Sha S
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
FAU - Du, Yimei
AU  - Du Y
AD  - Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, 
      Tongji Medical College, Huazhong University of Science and TechnologyWuhan, 
      China.
FAU - Chen, Lei
AU  - Chen L
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
AD  - Neuroprotective Drug Discovery Center, Nanjing Medical UniversityNanjing, China.
FAU - Chen, Ling
AU  - Chen L
AD  - Department of Physiology, Nanjing Medical UniversityNanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20170615
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5471311
OTO - NOTNLM
OT  - AMPK
OT  - Akt
OT  - TRPV4
OT  - calcium
OT  - dendritic arborization
EDAT- 2017/07/01 06:00
MHDA- 2017/07/01 06:01
PMCR- 2017/01/01
CRDT- 2017/07/01 06:00
PHST- 2017/02/22 00:00 [received]
PHST- 2017/05/29 00:00 [accepted]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2017/07/01 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00190 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Jun 15;10:190. doi: 10.3389/fnmol.2017.00190. 
      eCollection 2017.